(60 days)
ETEST® is a manual, quantitative technique for determination of antimicrobial susceptibility of non-fastidious Gram-negative and Gram-positive aerobic bacteria and fastidious bacteria. The system comprises a predefined antibiotic gradient which is used to determine the Minimum Inhibitory Concentration (MIC, in ug/mL) of different antimicrobial agents against microorganisms tested on agar media after overnight incubation.
Delafloxacin has been shown to be active against the aerobic microorganisms listed below according to the FDA label for this antimicrobial agent.
ETEST® DFX can be used to determine the MIC of Delafloxacin against the following microorganisms:
Active both in vitro and in clinical infections:
Gram-positive bacteria:
- · Staphylococcus aureus (including methicillin-resistant and methicillin-susceptible strains)
- Staphylococcus haemolyticus
- Staphylococcus lugdunensis
- Enterococcus faecalis
Gram-negative bacteria:
- Pseudomonas aeruginosa
ETEST® is a thin, inert and non-porous plastic strip carrying on one side the MIC reading scale in ug/mL, and on the other side a predefined antibiotic gradient.
When the strip is applied to an inoculated agar surface, the preformed antibiotic gradient immediately transfers into the agar matrix, then forming a stable, continuous and exponential gradient of antibiotic concentrations directly underneath the strip. Bacterial growth becomes visible during incubation, and a symmetrical inhibition ellipse centered along the strip appears. The MIC value is read from the scale in terms of ug/mL at complete inhibition of bacterial growth, where the pointed end of the ellipse intersects the strip.
ETEST® Delafloxacin contains a range of delafloxacin from 0.002 to 32 u2/mL.
This document describes the performance of the ETEST® Delafloxacin (DFX) device, a manual, quantitative technique for determining antimicrobial susceptibility. The study aims to demonstrate that the device is substantially equivalent to a predicate device (ETEST® Telavancin (TLA)) and meets pre-defined acceptance criteria based on established guidance and standards.
Here's a breakdown of the requested information:
1. A table of acceptance criteria and the reported device performance
The acceptance criteria are derived from the "FDA Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA, issued on August 28, 2009" and "CLSI M100-S29 January 2019". While specific numerical targets for Essential Agreement (EA) and Category Agreement (CA) are not explicitly stated as "acceptance criteria" percentages in the text, the performance data presented in the tables are implied to meet these criteria, as the conclusion states the device demonstrated "acceptable performance" and "substantially equivalent performance". The data strongly suggests typical FDA acceptance thresholds for AST devices, which often require high percentages.
| Performance Metric | Acceptance Criteria (Implied by FDA Guidance/CLSI) | Reported Device Performance (ETEST® Delafloxacin) |
|---|---|---|
| Essential Agreement (EA) | High percentage (e.g., typically >90%) | |
| Staphylococcus aureus | 96.5% | |
| Staphylococcus haemolyticus | 100.0% | |
| Staphylococcus lugdunensis | 100.0% | |
| Enterococcus faecalis | 100.0% | |
| Pseudomonas aeruginosa | 98.5% | |
| Category Agreement (CA) | High percentage (e.g., typically >90%) | |
| Staphylococcus aureus | 93.0% | |
| Staphylococcus haemolyticus | 93.5% | |
| Staphylococcus lugdunensis | Not applicable (no FDA breakpoints established) | Not applicable |
| Enterococcus faecalis | 96.1% | |
| Pseudomonas aeruginosa | 95.5% | |
| Reproducibility | High percentage (e.g., typically 100% for best-case/worst-case) | Best-case: 100% |
| Worst-case: 100% | ||
| Quality Control | Results within range > 95% of the times tested | Results within range > 95% of the times tested |
2. Sample size used for the test set and the data provenance
The document mentions "fresh and stock clinical isolates, as well as a set of challenge strains" were used for external evaluations. However, the specific sample sizes (number of isolates) for the test set are not provided in the document.
The data provenance implies a multi-center study ("External evaluations were conducted") and the use of clinical and challenge strains, suggesting a mix of real-world (clinical) and engineered (challenge) samples. The country of origin for the data is not explicitly stated, but the submitter's address is in France. The study appears to be prospective in nature for data collection, as it describes conducting evaluations for the purpose of this submission.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
This information is not provided in the document. The ground truth for antimicrobial susceptibility testing (AST) devices is typically established through a reference method.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
This information is not provided in the document. For AST devices, adjudication as typically understood for image-based diagnostic AI is not directly applicable. Instead, the "ground truth" is established by a well-defined and accepted reference method.
5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
No MRMC comparative effectiveness study was done or mentioned. This device is a manual, quantitative technique for antimicrobial susceptibility testing, not an AI-assisted diagnostic tool that would typically involve human reader performance improvement with AI.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
This refers to the performance of the ETEST® Delafloxacin device itself. The data presented in Table 1 ("Performance Characteristics for ETEST® Delafloxacin") represents the standalone performance of the device compared to the reference method. There is no "human-in-the-loop" component in the sense of an AI interpreting results and a human reviewing them; rather, a human reads the MIC value directly from the ETEST strip.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)
The ground truth for the performance study was established by the CLSI M07-A11 January 2018 broth microdilution reference method. This is considered the gold standard for determining Minimum Inhibitory Concentrations (MICs) in microbiology.
8. The sample size for the training set
The document does not specify a training set sample size. ETEST® products are physical diagnostic devices (strips), not machine learning algorithms that require a "training set" in the computational sense. The "training" for such devices would involve extensive research and development, and the performance is validated through studies like the one described.
9. How the ground truth for the training set was established
As there is no "training set" in the context of an AI algorithm, this question is not applicable. The development and optimization of the ETEST® system itself would have relied on established microbiological principles and validated methods for determining antimicrobial concentrations and their effects on bacterial growth.
§ 866.1640 Antimicrobial susceptibility test powder.
(a)
Identification. An antimicrobial susceptibility test powder is a device that consists of an antimicrobial drug powder packaged in vials in specified amounts and intended for use in clinical laboratories for determining in vitro susceptibility of bacterial pathogens to these therapeutic agents. Test results are used to determine the antimicrobial agent of choice in the treatment of bacterial diseases.(b)
Classification. Class II (performance standards).